Preclinical pharmacokinetics, pharmacodynamics, and toxicity of novel small-molecule GPR119 agonists to treat type-2 diabetes and obesity

The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target e...

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Vydané v:	Biomedicine & pharmacotherapy Ročník 177; s. 117077
Hlavní autori:	Patil, Mohan, Casari, Ilaria, Thapa, Dinesh, Warne, Leon N., Dallerba, Elena, Massi, Massimiliano, Carlessi, Rodrigo, Falasca, Marco
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	France Elsevier Masson SAS 01.08.2024
Predmet:	Animals Caco-2 Cells Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Enteroendocrine Cells - drug effects Enteroendocrine Cells - metabolism GLP-1 Glucagon-Like Peptide 1 - metabolism Humans Hypoglycemic Agents - pharmacokinetics Hypoglycemic Agents - pharmacology Male Mice Mice, Inbred C57BL obesity Obesity - drug therapy Obesity - metabolism pharmacodynamics pharmacokinetics Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - metabolism Synthetic GPR119 agonists toxicity type-2 diabetes toxicity MCV MMTT DMSO pharmacodynamics ALT LY AUC LC-MS/MS MPV RBC FBS CMC obesity EEC P-gp H&E T2D O-LPI Hr OEA GIP RA MCHC SEM BPM LPC Hpf W/v DPP-IV LPI GPR119 SAR Synthetic GPR119 agonists DMEM SD ANOVA Caco-2 GPCRs IpGTT pharmacokinetics WBC BUN AST GLP-1 type-2 diabetes ACN PEA PYY MCH Papp PD TPs TEER HBSS PK Kg
ISSN:	0753-3322, 1950-6007, 1950-6007
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